8JNI
Structure of AE2 in complex with PIP2
Summary for 8JNI
| Entry DOI | 10.2210/pdb8jni/pdb |
| EMDB information | 36448 |
| Descriptor | Anion exchange protein 2, CHLORIDE ION, [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate (3 entities in total) |
| Functional Keywords | ae2, slc4a2, pip2, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 276518.89 |
| Authors | |
| Primary citation | Zhang, W.,Ding, D.,Lu, Y.,Chen, H.,Jiang, P.,Zuo, P.,Wang, G.,Luo, J.,Yin, Y.,Luo, J.,Yin, Y. Structural and functional insights into the lipid regulation of human anion exchanger 2. Nat Commun, 15:759-759, 2024 Cited by PubMed Abstract: Anion exchanger 2 (AE2) is an electroneutral Na-independent Cl/HCO exchanger belongs to the SLC4 transporter family. The widely expressed AE2 participates in a variety of physiological processes, including transepithelial acid-base secretion and osteoclastogenesis. Both the transmembrane domains (TMDs) and the N-terminal cytoplasmic domain (NTD) are involved in regulation of AE2 activity. However, the regulatory mechanism remains unclear. Here, we report a 3.2 Å cryo-EM structure of the AE2 TMDs in complex with PIP and a 3.3 Å full-length mutant AE2 structure in the resting state without PIP. We demonstrate that PIP at the TMD dimer interface is involved in the substrate exchange process. Mutation in the PIP binding site leads to the displacement of TM7 and further stabilizes the interaction between the TMD and the NTD. Reduced substrate transport activity and conformation similar to AE2 in acidic pH indicating the central contribution of PIP to the function of AE2. PubMed: 38272905DOI: 10.1038/s41467-024-44966-0 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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